Previous work showed that incubation of fibroblasts with bradykinin (BK) at 37C markedly decreased the number of [3-H]BK-binding sites with little or no change in Kd for BK. The number of binding sites was also reduced by exposure (4-24 h) to dexamethasone (0.101 muM) or other corticosteroids with little or no change in Kd. Since corticosteroids are also known to inhibit release of arachidonate metabolites and production of prostaglandins, they can apparently reduce responsiveness to BK by receptor and post-receptor mechanisms. Increases in fibroblast cAMP content and changes in prostaglandin formation influenced by culture conditions or perhaps BK itself also affected BK responsiveness. Following addition of BK, PGD-2 formation increased, then rapidly declined. Following the decline, there was a rapid rise in PGE-2 and PGI-2 production and cAMP accumulation. Whereas exogenous PGE-2 and PGI-2 increased cAMP content, exogenous PGD-2 inhibited effects of BK on prostaglandin formation and cAMP accumulation, suggesting a role for PGD-2 modulating BK responsiveness. Using radiolabelling in conjunction with radioimmunoassay, we found that basal and BK-induced prostaglandin formation was derived primarily from slowly turning-over precursor pools and that BK stimulation caused hydrolysis of phosphatidylinositol-4,5-bisphosphate and phosphatidylinositol. In human fibroblasts, alterations in cGMP and cAMP accumulation and PGI-2 production in response to combinations of BK and nitroprusside (NP) differed quantitatively and temporally from the effects of BK and NP alone. In rat aortic and vena cava segments, different effects of NP and NG on cGMP content and PGI-2 production were consistent with differences in the effects of these two drugs on arterial and venous circulations.